Trial Title:
Tislelizumab in People With Colorectal Cancer
NCT ID:
NCT06529523
Condition:
Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Tislelizumab
Conditions: Keywords:
Tislelizumab
PD-1 blockade
24-063
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
This is a pilot, open label to gather preliminary data on the use of PD-1 blockade
therapy in patients with metastatic dMMR CRC (cohort 1) and patients with localized
(stage II/III) dMMR rectal cancer (cohort 2).
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tislelizumab
Description:
Patients will receive standard dose of tislelizumab 200mg IV flat dose q3weeks until
disease progression, unacceptable toxicity, patient/physician decides to withdraw
patient, death, or completion of 104 weeks treatment (35 administrations).
Arm group label:
Cohort 1: Stage 4 Colorectal cancer
Arm group label:
Cohort 2: Stage 2/3 Rectal cancer
Summary:
The researchers are doing this study to find out whether tislelizumab is an effective
treatment for people with colorectal cancer who are living in Nigeria. The researchers
will also look at the safety of the study drug.
All participants in this study will be treatment naïve (they have not yet received
treatment for their cancer), and their cancer will be mismatch repair deficient (dMMR).
dMMR cancer can happen when your cells are unable to repair mistakes made during the cell
division process.
Criteria for eligibility:
Criteria:
All subjects
Inclusion Criteria:
- Age 18 years or older on date of signing informed consent
- ECOG performance status of 0 or 1
- Negative pregnancy test done within 72 hours prior to start of treatment for women
of childbearing potential.
- Women of childbearing potential must be willing to use a highly effective
method of birth control for the duration of the study and for ≥ 120 days after
the last dose of tislelizumab They must also have a negative urine or serum
pregnancy test result ≤ 7 days before first dose of study drug.
- The Clinical Trials Facilitation Group recommendations related to contraception
and pregnancy testing in clinical studies include the use of highly effective
forms of birth control (Clinical Trials Facilitation Group 2014). These methods
include the following:
- Oral, intravaginal, or transdermal combined (estrogen- and
progestogen-containing) hormonal contraception associated with the
inhibition of ovulation
- Oral, injectable, implantable progestogen-only hormonal contraception
associated with the inhibition of ovulation Note: Oral birth control pills
are not considered a highly effective form of birth control, and if they
are selected, they must be used with a second, barrier method of
contraception such as condoms with or without spermicide.
- An intrauterine device
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Vasectomized partner Note: This is only considered a highly effective form
of birth control when the vasectomized partner is the sole partner of the
study participant and there has been a medical assessment confirming
surgical success.
- A sterile male is one for whom azoospermia, in a semen sample, has been
demonstrated as definitive evidence of infertility.
- Sexual abstinence (defined as refraining from heterosexual intercourse
during the entire period of risk associated with the study treatment)
Note: Total sexual abstinence should only be used as a contraceptive
method if it is in line with the patients' usual and preferred lifestyle.
Periodic abstinence (eg, calendar, ovulation, sympto-thermal, postovulation methods),
declaration of abstinence for the duration of exposure to study drug, and withdrawal are
not acceptable methods of contraception.
Of note, barrier contraception (including male and female condoms with or without
spermicide) is not considered a highly effective method of contraception; if used, this
method must be used in combination with one of the highly effective forms of birth
control listed above.
°"Women of non-childbearing potential" are defined as female patients meeting any of the
following criteria:
- Surgically sterile (ie, through bilateral salpingectomy, bilateral oophorectomy, or
hysterectomy)
- Postmenopausal, defined as:
- ≥ 55 years of age with no spontaneous menses for ≥ 12 months OR
- < 55 years of age with no spontaneous menses for ≥ 12 months AND with
postmenopausal follicle-stimulating hormone (FSH) concentration > 30 IU/mL and
all alternative medical causes for the lack of spontaneous menses for ≥ 12
months have been ruled out, such as polycystic ovarian syndrome,
hyperprolactinemia, etc.
- If an FSH measurement is required to confirm postmenopausal state, concomitant
use of hormonal contraception or hormonal replacement therapy should be
excluded.
[Adapted from Clinical Trials Facilitation Group (CTFG) 2014.]
- Nonsterile males must be willing to use a highly effective method of birth control
for the duration of the study and for ≥ 120 days after the last dose of tislelizumab
- A sterile male is defined as one for whom azoospermia has been previously
demonstrated in a semen sample examination as definitive evidence of
infertility.
- Males with known "low sperm counts" (consistent with "subfertility") are not to
be considered sterile.
- Demonstration of adequate organ function below within 14 days of cycle 1
day 1
- Cohort 1 subjects
- Histological confirmation of colorectal adenocarcinoma
- Confirmation of dMMR by immunohistochemistry
- Radiologically measurable metastatic disease as per RECIST 1.1, not eligible
for potentially curative surgery
- Cohort 2 subjects
- Histological confirmation of rectal adenocarcinoma
- Confirmation of dMMR by immunohistochemistry
- Rectal cancer stage II or III per AJCC 8 th edition criteria
- No evidence of distant metastases
- Hematological
- Absolute neutrophil count (ANC) ≥1,500 /mm^3
- Platelets ≥100,000 / mcL
- Hemoglobin >9 g/dL or ≥5.6 mmol/L
- Renal
- Serum creatinine OR measured or calculated creatinine clearance (GFR can also be
used in place of creatinine or CrCl) ≤1.5 × upper limit of normal (ULN) OR ≥30
mL/min for subject with creatinine levels > 1.5 × institutional ULN
- Hepatic
- Serum total bilirubin ≤ 1.5 × ULN OR Direct bilirubin ≤ ULN for subjects with total
bilirubin levels > 1.5 ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN (< 5 x ULN if hepatic metastases are present
in cohort 1
- Coagulation
- International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial
Thromboplastin Time (aPTT) INR <1.5 or PT <1.5 x ULN; and either PTT or aPTT <1.5 x
ULN. Patients on warfarin may be included on a stable dose with a therapeutic INR
<3.5
Exclusion Criteria:
- Presence of other active malignancy
- Diagnosis of immunodeficiency or receiving systemic steroid therapy or other
immunosuppressive therapy within 7 days prior to first dose of treatment
- Any condition that required systemic treatment with either corticosteroids (> 10 mg
daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days
before first dose of study drug. Inhaled or topical steroids, and adrenal
replacement doses > 10 mg daily prednisone equivalents are permitted in the absence
of an active autoimmune disease. Note: Patients who are currently or have previously
been on any of the following steroid regimens are not excluded:
1. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with
minimal systemic absorption
3. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for
contrast dye allergy) or for the treatment of a nonautoimmune condition (eg,
delayed-type hypersensitivity reaction caused by contact allergen
- Active autoimmune disease requiring systemic therapy within the 2 years prior to
treatment initiation
o Well controlled hypothyroidism, diabetes, and skin conditions allowed
- Untreated active Hepatitis B or Hepatitis C
o Patients actively on therapy with disease under control are allowed
- Untreated Acquired Immunodeficiency Syndrome (AIDS)
o Patients with Human Immunodeficiency Virus (HIV) well controlled on
anti-retroviral therapy are allowed
- Infection (including tuberculosis infection, etc.) requiring systemic (oral or
intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before first
dose of study drug
- History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled
lung diseases including pulmonary fibrosis.
o Patients with significantly impaired pulmonary function or who require
supplemental oxygen at baseline must undergo an assessment of pulmonary function at
screening
- Currently receiving other anticancer or experimental therapy
- Has received prior therapy with an immune checkpoint inhibitor
- Prior ≥ Grade 3 immune-related AE from previous immunotherapy
- Pregnant women, women who are breast-feeding, or men expecting to conceive or father
children during the trial period, through 120 days after last dose of medication
- Receipt of live vaccine within 30 days of planned treatment start
- Major surgical procedure or significant traumatic injury within 28 days prior to
enrollment
- Known hypersensitivity to Tislelizumab
- Prior allogeneic stem cell or organ transplantation
- Any of the following cardiovascular risk factors:
1. Cardiac chest pain, defined as moderate pain that limits instrumental
activities of daily living, ≤ 28 days before first dose of study drug
2. Pulmonary embolism ≤ 28 days before first dose of study drug
3. Any history of acute myocardial infarction ≤ 6 months before first dose of
study drug
4. Any history of heart failure meeting New York Heart Association Classification
III or IV ≤ 6 months before first dose of study drug
5. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before
first dose of study drug
6. Any history of cerebrovascular accident ≤ 6 months before first dose of study
drug
7. Uncontrolled hypertension that cannot be managed by standard antihypertension
medications ≤ 28 days before first dose of study drug
8. Any episode of syncope or seizure ≤ 28 days before first dose of study drug
- Cohort 1 subjects
- Prior immunotherapy, chemotherapy, radiation therapy, or surgery for metastatic
colorectal cancer
o Treatment with adjuvant therapy of prior localized tumor is allowable as long as
it was completed at least 6 months prior to cycle 1 day 1
- Known active central nervous system (CNS) metastasis and/or carcinomatous meningitis
o Patients with previously treated brain metastases may participate if the brain
metastases are stable via MRI assessment, performed ≥ 4 weeks after treatment
- Cohort 2 subjects
- Prior immunotherapy, chemotherapy, radiation therapy, or surgery for localized
rectal cancer
- Presence of metastatic or recurrent disease
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Fiyinfoliu Balogun, MD, PhD
Phone:
646-888-6964
Facility:
Name:
Lagos University Teaching Hospital
Address:
City:
Idi-Araba
Country:
Nigeria
Status:
Not yet recruiting
Contact:
Last name:
Fatimah Abdulkareem, MD
Phone:
08122167403
Facility:
Name:
Obafemi Awolowo University Teaching Hospital
Address:
City:
Ile-Ife
Country:
Nigeria
Status:
Not yet recruiting
Contact:
Last name:
Isaac Alatise, MD
Email:
segunalatishe@oau.edu.ng
Start date:
July 26, 2024
Completion date:
July 2028
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
BeiGene USA, Inc.
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06529523
http://www.mskcc.org/mskcc/html/44.cfm
